Sodium Acetate → ethyl 7-(acetyloxy)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-5-carboxylate

HRID 1880360Notes

Reaction equation

HRID 1880360 reaction equation
[CH2:1]([O:3][C:4](/[C:6](=[CH:11]/[C:12]1[CH:13]=[N:14][N:15]([CH:17]2[CH2:22][CH2:21][CH2:20][CH2:19][O:18]2)[CH:16]=1)/[CH2:7][C:8]([OH:10])=O)=[O:5])[CH3:2].[CH3:23][C:24]([O-])=[O:25].[Na+]>C(OC(=O)C)(=O)C>[C:24]([O:10][C:8]1[CH:7]=[C:6]([C:4]([O:3][CH2:1][CH3:2])=[O:5])[CH:11]=[C:12]2[C:16]=1[N:15]([CH:17]1[CH2:22][CH2:21][CH2:20][CH2:19][O:18]1)[N:14]=[CH:13]2)(=[O:25])[CH3:23]

Participants

4

Reactant 2

HCID 517045Sodium AcetateHCID 66920409(3E)-3-(ethoxycarbonyl)-4-[1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl]but-3-enoic acid

Product 1

HCID 66920401ethyl 7-(acetyloxy)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-5-carboxylateYield 26.8%

Reagents, catalysts & solvents 1

HCID 7918Acetic AnhydrideSolvent

Procedure

Crude (3E)-3-(ethoxycarbonyl)-4-[1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl]but-3-enoic acid (45 g) was mixed with acetic anhydride (500 mL) and NaOAc (12 g, 0.146 mol). The reaction mixture was heated at reflux over a period of 5 hours and evaporated. The residue was alkalized to pH 8-9 with aqueous Na2CO3. The product was extracted with EtOAc (5×50 mL). The combined extracts were dried and evaporated. The residue was purified by chromatography (EtOAc/hexane, 1:4) to provide ethyl 7-(acetyloxy)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-5-carboxylate (13 g, 25%).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux over a period of 5 hours
  3. customevaporated
  4. extractionThe product was extracted with EtOAc (5×50 mL)
  5. customThe combined extracts were dried
  6. customevaporated
  7. customThe residue was purified by chromatography (EtOAc/hexane, 1:4)

Sources & evidence

ORD record
ord-280753db9aca46f38215a951ea0bed2d
Source dataset
uspto-grants-2012_11
Patent number
US08318762B2

Reaction notes

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